The present invention relates to a novel process for the stereochemically controlled production of novel and known highly substituted azacyclic compounds and to novel intermediate products of this process. Furthermore, the invention relates to novel highly substituted azacyclic compounds which can be built up in isomerically pure manner and which have useful properties for numerous fields of application.
Highly substituted stereoisomers of azacyclic compounds, in particular highly substituted derivatives of pyrrolidines or piperidines, are useful starting materials for numerous applications, and are used, for example, as constituents of chiral catalysts in asymmetrical synthesis (see, e.g., Kobayashi et al., Chemistry Letters (=Chem. Lett.) (1991) 1341-1344), as constituents of biologically active alkaloids (see, e.g., Williams et al., Journal of Organic Chemistry (=JOC) 57 (1992) 6527-6532 and references cited therein; Jäger et al., Angewandte Chemie 102 (1990) 1180-1182) and as constituents of pharmacologically interesting compounds (see, e.g., Laschat et al., Synthesis 4 (1997) 475479). Furthermore, for example decahydroquinolines and pyrrolidines which can be produced according to the process of the invention or ones which are structurally closely related have interesting physiological effects (see, e.g., Kuzmitskii et al., Vestsi Akad. Navuk BSSR, Ser. Khim. Navuk 3 (1979) 82-85/Chemical Abstracts No. 91:117158c; Lash et al., Journal of Heterocyclic Chemistry 28 (1991) 1671-1676). The use of some of the pyrrolidines mentioned above for the production of porphyrin ring systems is also discussed therein. Processes for the production of such azacyclic compounds are also known in part from the literature sources quoted. Certain enantiomers of these compounds may be obtained according to the methods referred to therein usually by means of conventional racemate separation. However, production processes which are not in accordance with the invention are also mentioned, according to which selected individual compounds of substituted azacyclic compounds can be produced in isomerically pure manner. A general process for the stereo-controlled synthesis of isomerically pure, highly substituted azacyclic compounds is not known from the above literature sources.
Furthermore, the stereo-controlled synthesis of some tetrahydrofuran derivatives by reaction of 2-alkenyl sulfoximides with 2-tert. butyldimethyl-silyloxy-propanal (=TBS lactaldehyde) and subsequent fluoride-induced cyclisation is already known (see Reggelin et al., JACS 118 (1996) 4765-4777; Reggelin et al., Liebigs Annalen der Chemie/RECUEIL (1997) 1881-1886). However, highly substituted azacyclic compounds cannot be produced according to the process described therein.
The compound (2S,3S,4S,5S)-(N-tert.-butyloxycarbonyl)-2-benzyl-4,5-dimethyl-3-hydroxypyrrolidine is already known from the Internet publication at the address “www.iucr.ac.uk” by M. Bolte, Acta Crystallographica Section C, electronically published paper QA0017 [=(IUCr) Acta C Paper QA 0017]. The production of this compound is not described in the publication cited.